Summary: The nuclear hormone receptor retinoic acid-related orphan receptor (ROR)γt is required for the development of lymph nodes (LNs) and Peyer's patches (PPs), as these organs are absent in RORγt-deficient mice. During fetal life, RORγt is expressed exclusively in lymphoid tissue-inducer (LTi) cells, a cell type that localizes in developing LNs and PPs. LTi cells express surface lymphotoxin α1β2 that activates specialized mesenchymal cells to produce chemokines, upregulate adhesion molecules and induce further maturation of lymphoid organs. RORγt inhibits nuclear factor of activated T-cell (NFAT) function in cell lines and induces the expression of Bcl-xL and p27kip1 in the adult thymus, suggesting that RORγt prevents cell activation, cell-cycle progression, and apoptosis. We propose that RORγt, together with the inhibitor of basic helix-loop-helix transcription factor Id2, ensures generation and survival of fetal LTi cells necessary for the development of LNs and PPs.